RHD*04.03 - RHD*DIV.3
(ISBT table: RHD partial D v5.0)

This entry is an hybrid RHD allele.

DIV type 3, DIVb type 3 (obsolete), RHD*D-CE(6-9)-D, RHD*D-CE(6-9)-D (DIV type 3), RHD-RHCE(6-9)-RHD,
Download VCF file

Molecular data

Nucleotides: 916G>A; 932A>G; 941G>T; 968C>A; 974G>T; 979A>G; 985GG>CA deletion-insertion; 989A>C; 992A>T; 1025T>C; 1048G>C; 1053C>T; 1057GGA>TGG deletion-insertion; 1060GC>AA deletion-insertion; 1170T>C; 1193A>T;

Amino acids: V306I; Y311C; G314V; P323H; S325I; I327V; G329H; Y330S; N331I; I342T; D350H; T351T; G353W; A354N; L390L; E398V;

Hybrid allele encompassing at least one RHCE exon: RHD-RHCE(6-9)-RHD

Comments on the molecular basis:

  • "The 3′ breakpoint was confirmed (n = 6) as described previously (in 9864185)"

Extracellular position of one or more amino acid substitutions:

  • membrane localization: EF, TM and IC

Splicing:

Unconventional prediction methods:

Phenotype

Main D phenotype: variable/discrepant (last update: Nov. 11, 2019)
Reports by D phenotype
Other RH phenotypes: RH:-3, -4, -30,
  • RH:-3 inferred from the reported RHCE phenotypes of the carriers
  • RH:-4 inferred from the reported RHCE phenotypes of the carriers
  • RH:-30
Serology with monoclonal anti-D
  • more than 10 monoclonal IgG anti-D non-reactive with variant, out of 60 monoclonal IgG anti 22 IgM anti-D tested (same sample as 9864185)
  • 83 anti-D tested; epitope pattern; many epitopes missing (Table1)
  • more than 5 anti-D non-reactive with variant, out of approx 20 monoclonal IgG tested (Table 3)
Antigen Density (Ag/RBC)
  • 607 Ag/RBC, 1 RH:1,2,-3,-4,5 sample with possible suppressive effect of dCe in trans; derived from the results obtained with 17 of the 59 monoclonal IgG anti-D tested
  • 4544 Ag/RBC, 1 sample (control) (data reproduced from 12200394)
More phenotype data
Rhesus Similarity Index

  • 0.0 (1 RH:1,2,-3,-4,5 sample with possible suppressive effect of dCe in trans; derived from the results obtained with 17 of the 59 monoclonal IgG anti-D tested)

Haplotype

Main CcEe phenotype association: Ce (last update: Dec. 20, 2019)
Number of samples reported by haplotype
ce Ce cE CE
ce 0 6 0 0
Ce 4 1 0
cE 0 0
CE 0
Reports by CcEe phenotype
  • with Ccee
    • 1 sample
    5 samples
  • with Ce
    • 3 samples
    1 sample (haplotype given, not complete phenotype)
    0 samples (Table 2; presented as a general association)
  • with CcEe
    • 1 sample
Main allele association:
Reports by allele association

Alloimmunization

Antibodies in carriers
Antibody specificity: D (RH1)
Summary: allo-anti-D (last update: Nov. 17, 2019)
Detailed information
    von Zabern I et al. Transfusion (2013) (Table 2)
    Wagner FF et al. Transfus Med Hemother (2014) (RIR n°23)
  • Ab specificity: D (RH1)
  • Number (auto- or allo-):
  • Number listed as allo-: 1
  • Number listed as auto-:
  • Number of carriers of the allele assessed:
  • DAT: negative
  • Autologuous control: ND
  • Elution: ND
  • Autoadsorption: ND
  • Titer: 1
  • Was anti-LW excluded?: yes
  • Other antibodies detected: anti-E
  • Cross matches (with Ab and RBCs from different partial types): ND
  • Transfusion history: none
  • Pregnancy history:
  • Anti-D Ig history: ND, probably none
  • Context: ND
  • Hemolytic consequences: ND
  • Comment:
    von Zabern I et al. Transfusion (2013) (Table 2)
    Wagner FF et al. Transfus Med Hemother (2014) (RIR n°26)
  • Ab specificity: D (RH1)
  • Number (auto- or allo-):
  • Number listed as allo-: 1
  • Number listed as auto-:
  • Number of carriers of the allele assessed:
  • DAT: negative
  • Autologuous control: ND
  • Elution: ND
  • Autoadsorption: ND
  • Titer: 2
  • Was anti-LW excluded?: yes
  • Other antibodies detected: anti-E
  • Cross matches (with Ab and RBCs from different partial types): ND
  • Transfusion history: unknown
  • Pregnancy history:
  • Anti-D Ig history: ND, probably none
  • Context: ND
  • Hemolytic consequences: ND
  • Comment:
    von Zabern I et al. Transfusion (2013) (Table 2)
    Wagner FF et al. Transfus Med Hemother (2014) (RIR n°94)
  • Ab specificity: D (RH1)
  • Number (auto- or allo-):
  • Number listed as allo-: 1
  • Number listed as auto-:
  • Number of carriers of the allele assessed:
  • DAT: positive
  • Autologuous control: ND
  • Elution: negative
  • Autoadsorption: ND
  • Titer: 8
  • Was anti-LW excluded?: yes
  • Other antibodies detected: ND
  • Cross matches (with Ab and RBCs from different partial types): ND
  • Transfusion history: 2 D+ RBC units
  • Pregnancy history:
  • Anti-D Ig history: ND, probably none
  • Context: ND
  • Hemolytic consequences: ND
  • Comment:
Antibodies in D negative recipients

Alloimmunization in recipients: expected to be possible, see phenotype data

Reports

Summary: few descriptions, mainly in the German population (last update: Dec. 20, 2019)
Detailed reports
  • 1/161 random donors with weak D phenotype; DVI samples were excluded by serologic testing in the German population (Southwestern Germany), White
  • 1 sample donor in the German population, Baden-Wuttemberg
  • 4/78156 (8 were RHef00606 and characterized further) donations, of which 60965 had D positive phenotype. 8 donors with RHef00606 were detected by serologic screening and further characterized by molecular analysis. 4 of those were RHef00069 In the German population, Southwestern Germany.
  • 1 sample Caucasian, Swiss
  • 2 samples Caucasian, German
Allele or phenotype frequency
  • 1/32448 estimated allele frequency in the German population (Southwestern Germany), White
  • 1/19539 (CI: 1/8143 - 1/57215) estimated phenotype frequency among 78156 blood donations of which 60965 had D positive phenotype in the German population, southwestern Germany

2D diagram

generated using Protter extraintra Met1 Met1 Ser2 Ser2 Ser3 Ser3 Lys4 Lys4 Tyr5 Tyr5 Pro6 Pro6 Arg7 Arg7 Ser8 Ser8 Val9 Val9 Arg10 Arg10 10Arg11 Arg11 Cys12 Cys12 Leu13 Leu13 Pro14 Pro14 Leu15 Leu15 Trp16 Trp16 Ala17 Ala17 Leu18 Leu18 Thr19 Thr19 Leu20 Leu20 20Glu21 Glu21 Ala22 Ala22 Ala23 Ala23 Leu24 Leu24 Ile25 Ile25 Leu26 Leu26 Leu27 Leu27 Phe28 Phe28 Tyr29 Tyr29 Phe30 Phe30 30Phe31 Phe31 Thr32 Thr32 His33 His33 Tyr34 Tyr34 Asp35 Asp35 Ala36 Ala36 Ser37 Ser37 Leu38 Leu38 Glu39 Glu39 Asp40 Asp40 40Gln41 Gln41 Lys42 Lys42 Gly43 Gly43 Leu44 Leu44 Val45 Val45 Ala46 Ala46 Ser47 Ser47 Tyr48 Tyr48 Gln49 Gln49 Val50 Val50 50Gly51 Gly51 Gln52 Gln52 Asp53 Asp53 Leu54 Leu54 Thr55 Thr55 Val56 Val56 Met57 Met57 Ala58 Ala58 Ala59 Ala59 Ile60 Ile60 60Gly61 Gly61 Leu62 Leu62 Gly63 Gly63 Phe64 Phe64 Leu65 Leu65 Thr66 Thr66 Ser67 Ser67 Ser68 Ser68 Phe69 Phe69 Arg70 Arg70 70Arg71 Arg71 His72 His72 Ser73 Ser73 Trp74 Trp74 Ser75 Ser75 Ser76 Ser76 Val77 Val77 Ala78 Ala78 Phe79 Phe79 Asn80 Asn80 80Leu81 Leu81 Phe82 Phe82 Met83 Met83 Leu84 Leu84 Ala85 Ala85 Leu86 Leu86 Gly87 Gly87 Val88 Val88 Gln89 Gln89 Trp90 Trp90 90Ala91 Ala91 Ile92 Ile92 Leu93 Leu93 Leu94 Leu94 Asp95 Asp95 Gly96 Gly96 Phe97 Phe97 Leu98 Leu98 Ser99 Ser99 Gln100 Gln100 100Phe101 Phe101 Pro102 Pro102 Ser103 Ser103 Gly104 Gly104 Lys105 Lys105 Val106 Val106 Val107 Val107 Ile108 Ile108 Thr109 Thr109 Leu110 Leu110 110Phe111 Phe111 Ser112 Ser112 Ile113 Ile113 Arg114 Arg114 Leu115 Leu115 Ala116 Ala116 Thr117 Thr117 Met118 Met118 Ser119 Ser119 Ala120 Ala120 120Leu121 Leu121 Ser122 Ser122 Val123 Val123 Leu124 Leu124 Ile125 Ile125 Ser126 Ser126 Val127 Val127 Asp128 Asp128 Ala129 Ala129 Val130 Val130 130Leu131 Leu131 Gly132 Gly132 Lys133 Lys133 Val134 Val134 Asn135 Asn135 Leu136 Leu136 Ala137 Ala137 Gln138 Gln138 Leu139 Leu139 Val140 Val140 140Val141 Val141 Met142 Met142 Val143 Val143 Leu144 Leu144 Val145 Val145 Glu146 Glu146 Val147 Val147 Thr148 Thr148 Ala149 Ala149 Leu150 Leu150 150Gly151 Gly151 Asn152 Asn152 Leu153 Leu153 Arg154 Arg154 Met155 Met155 Val156 Val156 Ile157 Ile157 Ser158 Ser158 Asn159 Asn159 Ile160 Ile160 160Phe161 Phe161 Asn162 Asn162 Thr163 Thr163 Asp164 Asp164 Tyr165 Tyr165 His166 His166 Met167 Met167 Asn168 Asn168 Met169 Met169 Met170 Met170 170His171 His171 Ile172 Ile172 Tyr173 Tyr173 Val174 Val174 Phe175 Phe175 Ala176 Ala176 Ala177 Ala177 Tyr178 Tyr178 Phe179 Phe179 Gly180 Gly180 180Leu181 Leu181 Ser182 Ser182 Val183 Val183 Ala184 Ala184 Trp185 Trp185 Cys186 Cys186 Leu187 Leu187 Pro188 Pro188 Lys189 Lys189 Pro190 Pro190 190Leu191 Leu191 Pro192 Pro192 Glu193 Glu193 Gly194 Gly194 Thr195 Thr195 Glu196 Glu196 Asp197 Asp197 Lys198 Lys198 Asp199 Asp199 Gln200 Gln200 200Thr201 Thr201 Ala202 Ala202 Thr203 Thr203 Ile204 Ile204 Pro205 Pro205 Ser206 Ser206 Leu207 Leu207 Ser208 Ser208 Ala209 Ala209 Met210 Met210 210Leu211 Leu211 Gly212 Gly212 Ala213 Ala213 Leu214 Leu214 Phe215 Phe215 Leu216 Leu216 Trp217 Trp217 Met218 Met218 Phe219 Phe219 Trp220 Trp220 220Pro221 Pro221 Ser222 Ser222 Phe223 Phe223 Asn224 Asn224 Ser225 Ser225 Ala226 Ala226 Leu227 Leu227 Leu228 Leu228 Arg229 Arg229 Ser230 Ser230 230Pro231 Pro231 Ile232 Ile232 Glu233 Glu233 Arg234 Arg234 Lys235 Lys235 Asn236 Asn236 Ala237 Ala237 Val238 Val238 Phe239 Phe239 Asn240 Asn240 240Thr241 Thr241 Tyr242 Tyr242 Tyr243 Tyr243 Ala244 Ala244 Val245 Val245 Ala246 Ala246 Val247 Val247 Ser248 Ser248 Val249 Val249 Val250 Val250 250Thr251 Thr251 Ala252 Ala252 Ile253 Ile253 Ser254 Ser254 Gly255 Gly255 Ser256 Ser256 Ser257 Ser257 Leu258 Leu258 Ala259 Ala259 His260 His260 260Pro261 Pro261 Gln262 Gln262 Gly263 Gly263 Lys264 Lys264 Ile265 Ile265 Ser266 Ser266 Lys267 Lys267 Thr268 Thr268 Tyr269 Tyr269 Val270 Val270 270His271 His271 Ser272 Ser272 Ala273 Ala273 Val274 Val274 Leu275 Leu275 Ala276 Ala276 Gly277 Gly277 Gly278 Gly278 Val279 Val279 Ala280 Ala280 280Val281 Val281 Gly282 Gly282 Thr283 Thr283 Ser284 Ser284 Cys285 Cys285 His286 His286 Leu287 Leu287 Ile288 Ile288 Pro289 Pro289 Ser290 Ser290 290Pro291 Pro291 Trp292 Trp292 Leu293 Leu293 Ala294 Ala294 Met295 Met295 Val296 Val296 Leu297 Leu297 Gly298 Gly298 Leu299 Leu299 Val300 Val300 300Ala301 Ala301 Gly302 Gly302 Leu303 Leu303 Ile304 Ile304 Ser305 Ser305 Val306 Val306 Gly307 Gly307 Gly308 Gly308 Ala309 Ala309 Lys310 Lys310 310Tyr311 Tyr311 Leu312 Leu312 Pro313 Pro313 Gly314 Gly314 Cys315 Cys315 Cys316 Cys316 Asn317 Asn317 Arg318 Arg318 Val319 Val319 Leu320 Leu320 320Gly321 Gly321 Ile322 Ile322 Pro323 Pro323 His324 His324 Ser325 Ser325 Ser326 Ser326 Ile327 Ile327 Met328 Met328 Gly329 Gly329 Tyr330 Tyr330 330Asn331 Asn331 Phe332 Phe332 Ser333 Ser333 Leu334 Leu334 Leu335 Leu335 Gly336 Gly336 Leu337 Leu337 Leu338 Leu338 Gly339 Gly339 Glu340 Glu340 340Ile341 Ile341 Ile342 Ile342 Tyr343 Tyr343 Ile344 Ile344 Val345 Val345 Leu346 Leu346 Leu347 Leu347 Val348 Val348 Leu349 Leu349 Asp350 Asp350 350Thr351 Thr351 Val352 Val352 Gly353 Gly353 Ala354 Ala354 Gly355 Gly355 Asn356 Asn356 Gly357 Gly357 Met358 Met358 Ile359 Ile359 Gly360 Gly360 360Phe361 Phe361 Gln362 Gln362 Val363 Val363 Leu364 Leu364 Leu365 Leu365 Ser366 Ser366 Ile367 Ile367 Gly368 Gly368 Glu369 Glu369 Leu370 Leu370 370Ser371 Ser371 Leu372 Leu372 Ala373 Ala373 Ile374 Ile374 Val375 Val375 Ile376 Ile376 Ala377 Ala377 Leu378 Leu378 Met379 Met379 Ser380 Ser380 380Gly381 Gly381 Leu382 Leu382 Leu383 Leu383 Thr384 Thr384 Gly385 Gly385 Leu386 Leu386 Leu387 Leu387 Leu388 Leu388 Asn389 Asn389 Leu390 Leu390 390Lys391 Lys391 Ile392 Ile392 Trp393 Trp393 Lys394 Lys394 Ala395 Ala395 Pro396 Pro396 His397 His397 Glu398 Glu398 Ala399 Ala399 Lys400 Lys400 400Tyr401 Tyr401 Phe402 Phe402 Asp403 Asp403 Asp404 Asp404 Gln405 Gln405 Val406 Val406 Phe407 Phe407 Trp408 Trp408 Lys409 Lys409 Phe410 Phe410 410Pro411 Pro411 His412 His412 Leu413 Leu413 Ala414 Ala414 Val415 Val415 Gly416 Gly416 Phe417 Phe417 417 MSSKYPRSVRRCLPLWALTLEAALILLFYFFTHYDASLEDQKGLVASYQVGQDLTVMAAIGLGFLTSSFRRHSWSSVAFNLFMLALGVQWAILLDGFLSQFPSGKVVITLFSIRLATMSALSVLISVDAVLGKVNLAQLVVMVLVEVTALGNLRMVISNIFNTDYHMNMMHIYVFAAYFGLSVAWCLPKPLPEGTEDKDQTATIPSLSAMLGALFLWMFWPSFNSALLRSPIERKNAVFNTYYAVAVSVVTAISGSSLAHPQGKISKTYVHSAVLAGGVAVGTSCHLIPSPWLAMVLGLVAGLISVGGAKYLPGCCNRVLGIPHSSIMGYNFSLLGLLGEIIYIVLLVLDTVGAGNGMIGFQVLLSIGELSLAIVIALMSGLLTGLLLNLKIWKAPHEAKYFDDQVFWKFPHLAVGF MSSKYPRSVRRCLPLWALTLEAALILLFYFFTHYDASLEDQKGLVASYQVGQDLTVMAAIGLGFLTSSFRRHSWSSVAFNLFMLALGVQWAILLDGFLSQFPSGKVVITLFSIRLATMSALSVLISVDAVLGKVNLAQLVVMVLVEVTALGNLRMVISNIFNTDYHMNMMHIYVFAAYFGLSVAWCLPKPLPEGTEDKDQTATIPSLSAMLGALFLWMFWPSFNSALLRSPIERKNAVFNTYYAVAVSVVTAISGSSLAHPQGKISKTYVHSAVLAGGVAVGTSCHLIPSPWLAMVLGLVAGLISVGGAKYLPGCCNRVLGIPHSSIMGYNFSLLGLLGEIIYIVLLVLDTVGAGNGMIGFQVLLSIGELSLAIVIALMSGLLTGLLLNLKIWKAPHEAKYFDDQVFWKFPHLAVGF MSSKYPRSVRRCLPLWALTLEAALILLFYFFTHYDASLEDQKGLVASYQVGQDLTVMAAIGLGFLTSSFRRHSWSSVAFNLFMLALGVQWAILLDGFLSQFPSGKVVITLFSIRLATMSALSVLISVDAVLGKVNLAQLVVMVLVEVTALGNLRMVISNIFNTDYHMNMMHIYVFAAYFGLSVAWCLPKPLPEGTEDKDQTATIPSLSAMLGALFLWMFWPSFNSALLRSPIERKNAVFNTYYAVAVSVVTAISGSSLAHPQGKISKTYVHSAVLAGGVAVGTSCHLIPSPWLAMVLGLVAGLISVGGAKYLPGCCNRVLGIPHSSIMGYNFSLLGLLGEIIYIVLLVLDTVGAGNGMIGFQVLLSIGELSLAIVIALMSGLLTGLLLNLKIWKAPHEAKYFDDQVFWKFPHLAVGF MSSKYPRSVRRCLPLWALTLEAALILLFYFFTHYDASLEDQKGLVASYQVGQDLTVMAAIGLGFLTSSFRRHSWSSVAFNLFMLALGVQWAILLDGFLSQFPSGKVVITLFSIRLATMSALSVLISVDAVLGKVNLAQLVVMVLVEVTALGNLRMVISNIFNTDYHMNMMHIYVFAAYFGLSVAWCLPKPLPEGTEDKDQTATIPSLSAMLGALFLWMFWPSFNSALLRSPIERKNAVFNTYYAVAVSVVTAISGSSLAHPQGKISKTYVHSAVLAGGVAVGTSCHLIPSPWLAMVLGLVAGLISVGGAKYLPGCCNRVLGIPHSSIMGYNFSLLGLLGEIIYIVLLVLDTVGAGNGMIGFQVLLSIGELSLAIVIALMSGLLTGLLLNLKIWKAPHEAKYFDDQVFWKFPHLAVGF

Structure mapping

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Links

The Human RhesusBase
Genbank: HF549087
Erythrogene

References

  1. Wagner FF et al. Molecular basis of weak D phenotypes. Blood, 1999. [Citation] [RHeference]
  2. Avent ND et al. The rhesus blood group system: insights from recent advances in molecular biology. Transfus Med Rev, 1999. [Citation] [RHeference]
  3. Wagner FF et al. Weak D alleles express distinct phenotypes. Blood, 2000. [Citation] [RHeference]
  4. Wagner FF et al. DNB: a partial D with anti-D frequent in Central Europe. Blood, 2002. [Citation] [RHeference]
  5. von Zabern I et al. D category IV: a group of clinically relevant and phylogenetically diverse partial D. Transfusion, 2013. [Citation] [RHeference]
  6. Daniels G et al. Variants of RhD--current testing and clinical consequences. Br J Haematol, 2013. [Citation] [RHeference]
  7. Wagner FF et al. The Rhesus Site. Transfus Med Hemother, 2014. [Citation] [RHeference]
  8. Floch A et al. Comment from Rheference Online ressource, 2020. — Online ressource — [RHeference]

Last update: June 30, 2020